Association between maternal blood lipids during pregnancy and offspring growth trajectories in a predominantly macrosomic cohort: findings from the ROLO longitudinal birth cohort study.

The purpose of this study is to examine associations between maternal lipid profiles in pregnancy and offspring growth trajectories in a largely macrosomic cohort. This is a secondary analysis of the ROLO birth cohort (n = 293), which took place in the National Maternity Hospital, Dublin, Ireland. Infants were mostly macrosomic, with 55% having a birthweight > 4 kg. Maternal mean age was 32.4 years (SD 3.9 years), mean BMI was 26.1 kg/m2 (SD 4.4 kg/m2) and 48% of children born were males. Total cholesterol, high density lipoprotein cholesterol (HDL-cholesterol), low density lipoprotein cholesterol (LDL-cholesterol) and triglycerides were measured from fasting blood samples of mothers at 14 and 28 week gestation. The change in maternal lipid levels from early to late pregnancy was also examined. Offspring abdominal circumference and weight were measured at 20- and 34-week gestation, birth, 6 months, 2 years and 5 years postnatal. Linear spline multilevel models examined associations between maternal blood lipid profiles and offspring growth. We found some weak, significant associations between maternal blood lipids and trajectories of offspring growth. Significant findings were close to the null, providing limited evidence. For instance, 1 mmol/L increase in maternal triglycerides was associated with faster infant weight growth from 20- to 34-week gestation (0.01 kg/week, 95% CI - 0.02, - 0.001) and slower abdominal circumference from 2 to 5 years (0.01 cm/week, 95% CI - 0.02, - 0.001). These findings do not provide evidence of a clinically meaningful effect.    Conclusion: These findings raise questions about the efficacy of interventions targeting maternal blood lipid profiles in pregnancies at risk of macrosomia. New studies on this topic are needed. What is Known: • Maternal fat accumulation during early pregnancy may potentially support fetal growth in the third trimester by providing a reserve of lipids that are broken down and transferred to the infant across the placental barrier. • There are limited studies exploring the impact of maternal lipid profiles on infant and child health using growth trajectories spanning prenatal to postnatal life. What is New: • Maternal blood lipid profiles were not associated with offspring growth trajectories of weight and abdominal circumference during pregnancy up to 5 years of age in a largely macrosomic cohort, as significant findings were close to the null, providing limited evidence for a clinically meaningful relationship. • Strengths of this work include the use of infant growth trajectories that span prenatal to postnatal life and inclusion of analyses of the change of maternal lipid levels from early to late pregnancy and their associations with offspring growth trajectories from 20-week gestation to 5 years of age.

Admission patterns in a psychiatric intensive care unit in Ireland: a longitudinal follow-up.

OBJECTIVE: This study aims to describe the course of admission and clinical characteristics of admissions to a psychiatric intensive care unit (PICU) in the Phoenix Care Centre (PCC), Dublin, Ireland. METHODS: This retrospective chart study was conducted at the PCC, Dublin, Ireland. The cohort included all admission episodes (n = 91 complete data) over a three-year study period between January 2014 and January 2017. RESULTS: The mean age of admitted cases was 37.1 (s.d. = 11.3; range 18-63). The mean length of stay (LOS) was 59.3 days (s.d. = 61.0; median 39.5 days). All patients were admitted under Mental Health Act legislation. Antipsychotic polypharmacy was used in 61% (n = 55) of the admissions. A diagnosis of acute psychotic disorder (B = -1.027, p = 0.003, 95% CI: -1.691, -0.363) was associated with reduced LOS in PICU. CONCLUSION: Our study describes the cohort of patients admitted as being predominantly male, younger-aged, single, having a diagnosis of schizophrenia and being legally detained. The primary indication for referral is risk of assault, which highlights the need for the intensive and secure treatment model that a PICU can provide.

DASH (Dietary Approaches to Stop Hypertension) dietary pattern and maternal blood pressure in pregnancy.

BACKGROUND: High blood pressure (BP) in pregnancy is associated with significant adverse outcomes. In nonpregnant populations, the DASH (Dietary Approaches to Stop Hypertension) diet is associated with reductions in blood pressure. The present study investigated the relationship between the DASH dietary pattern and maternal BP in pregnancy. METHODS: This is an observational study of 511 women who participated in the ROLO study (Randomized cOntrol trial of LOw glycaemic index diet for the prevention of recurrence of macrosomia), 2007-2011, Dublin, Ireland. Auscultatory blood pressure, systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements were taken. Mean arterial pressure (MAP) was calculated. Dietary intakes were recorded using 3-day food diaries in each trimester. DASH scoring criteria were used to score and rank participants from low to high intakes of foods recommended in the DASH diet. Statistical analysis using analysis of variance and multiple linear regression were used to determine the relationship between maternal BP and DASH scores. RESULTS: Dietary intake more closely resembling the DASH dietary recommendations throughout pregnancy was associated with a lower DBP (mmHg) in trimesters 1 [B: -0.70; 95% confidence interval (CI) = -1.21 to -0.18] and 3 (B: -0.68; 95% CI = -1.19 to -0.17), as well as lower MAP (mmHg) in trimesters 1 (B: -0.78; 95% CI = -1.33 to -0.25) and 3 (B: -0.54; 95% CI = -1.04 to -0.04), controlling for body mass index, age, education, energy intake and intervention grouping. CONCLUSIONS: The DASH dietary pattern was associated with lower maternal BP in pregnancy among healthy women without hypertensive disorders of pregnancy. Despite the observational nature of these findings, the results demonstrate the potential for healthcare professionals to intervene to promote cardiovascular health in pregnancy.

Biotin supplementation causes erroneous elevations of results in some commercial serum 25-hydroxyvitamin d (25OHD) assays.

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes serum samples globally, on a quarterly basis, to assess participants' performance of specific methods for 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D). DEQAS occasionally circulates samples containing high levels of substances found in certain clinical situations e.g. 25-OHD2, 24,25-(OH)2D3, hypertriglyceridemia. The increased availability and use of health supplements containing biotin has led to case reports of assay interference in methods utilizing a biotin-streptavidin detection system. In October 2018, DEQAS included a serum sample (545) containing exogenous biotin (concentration =586 µg/L) which was analyzed by a total of 683 laboratories using 35 different methods. The same serum sample (544) without exogenous biotin was also included in the 5-sample set. All methods (760 laboratories) performed satisfactorily on sample 544 giving an All-Laboratory Trimmed Mean = 50.2 ± 6.5 nmol/L (±SD, CV = 12.9 %). The target value for this sample 544 (& 555) was 47.4 nmol/L as determined by Centers for Disease Control and Prevention (CDC) Atlanta, Georgia using their LC-MS/MS reference method. In contrast, #545 containing the exogenous biotin was reported by only 683 laboratories and gave an All-Laboratory Trimmed Mean = 66.8 ± 37.6 nmol/L (±SD, CV = 56.3 %). As expected, LC-MS/MS methods (143 labs) reported similar results for both 544 = 48.9 ± 4.4 nmol/L (±SD) and 545 = 48.3 ± 4.5 nmol/L (±SD) showing that assays involving chromatographic steps are unaffected by the presence of biotin. Several of the antibody-based assays including Abbott Architect, DiaSorin Liaison, Beckman Unicel and Siemens Centaur are also unaffected by the addition of biotin. Two assays, IDS-iSYS and Roche Total 25OHD, both of which use biotin-streptavidin, exhibit biotin interference yielding values with a significant positive bias for 545 of 102.6 nmol/L ± 78.7 nmol/L (±SD) and 517.8 nmol/L ± 209.8 nmol/L (±SD) respectively. Interestingly, the failure to report sample 545 data from 77 laboratories is due solely to those running Roche Total 25OHD or Roche Vitamin D Total II assays. Given the prevalence of the adversely affected assays (25 % of DEQAS users) and the high volume of 25OHD testing, clinicians using these assays should, where possible, only measure 25OHD when patients are off biotin.

Anorexia Nervosa with Markedly High Bone Turnover and Hyperphosphatemia During Refeeding Rectified by Denosumab.

We describe a unique case of hyperphosphatemia associated with a very high bone turnover rate in a 51-year-old postmenopausal woman with undiagnosed anorexia nervosa (AN) who presented with a low-trauma hip fracture. In view of her severely malnourished state, she was not fit for surgery. She was treated according to a refeeding protocol that mandated bed rest. Contrary to expectation, she developed sustained hyperphosphatemia and borderline hypercalcemia. Bone remodelling markers, both resorption and formation, were markedly elevated. Parathyroid hormone (PTH) was low-normal at 1.7 pmol/L, C-terminal fibroblast growth factor 23 (FGF23) was high at 293 RU/ml, but tubular maximum reabsorption of phosphate (TmPO4/GFR) was elevated at 1.93 mmol/L. Denosumab 60 mg was administered that was followed by: rapid normalisation of serum phosphate; normalisation of resorption markers, transient hypocalcaemia with secondary hyperparathyroidism, and normalisation of both TmPO4/GFR and C-terminal FGF23. We speculate that prolonged immobilization as part of AN management led to a high remodelling state followed by hyperphosphatemia and high-normal calcium with appropriate suppression of PTH and that marked hyperphosphatemia and high TmP/GFR despite high FGF23 indicates the necessity of PTH adequacy for excess FGF23 to lower TmP/GFR.

Estimating uncertainty of target values for DEQAS serum materials.

The External Quality Assessment (EQA) scheme for vitamin D metabolites (DEQAS) distributes human serum samples to laboratories across the world to assess their performance in measuring serum total 25-hydroxyvitamin D [25(OH)D], i.e. the sum of the concentrations of serum 25(OH)D2 and 25(OH)D3. In 2013 DEQAS, in collaboration with the Vitamin D Standardization Program (VDSP), became an accuracy-based EQAS when the National Institute for Standards and Technology (NIST) began assigning 25(OH)D target values to DEQAS serum samples using their Joint Committee for Traceability in Laboratory Medicine (JCTLM) approved reference measurement procedure (RMP). Historically, NIST has performed 4 determinations of 25-OHD2 and 25-OHD3 on each sample and used the mean values to calculate a single 'target value' for Total 25-OHD against which performance was judged. By definition the target values cannot be exact and each is associated with a level of uncertainty. The total uncertainty (UNIST) has two components, one from the 25(OH)D2, and 25(OH)D3 measurements and the other associated with the calibration procedure. The total combined uncertainty is calculated by adding up these uncertainties. In future, uncertainties will be attached to the target value in each DEQAS serum sample, starting with the next distribution cycle in 2019. Confidence intervals obtained using these uncertainties will allow DEQAS participants to determine if their result agrees with the NIST assigned target value. Furthermore, if the value falls within the confidence interval the laboratory's assay would be regarded as traceable, i.e. standardized, to the NIST RMP.

External Quality Assessment of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) assays.

The discovery that mutations of the CYP24A1 gene are a cause of idiopathic infantile hypercalcemia (IIH) has revived interest in measuring serum 24,25(OH)2D3. Several studies have also suggested that a high 25-hydroxyvitamin D3(25-OHD3):24,25(OH)2D3 ratio might provide additional diagnostic information in the investigation of vitamin D deficiency. Measurement of 24,25(OH)2D3 is necessarily restricted to laboratories with mass spectrometry methods although cross reactivity of the metabolite in immunoassays for 25-OHD is a potential cause of misleading results. The international External Quality Assessment (EQA) scheme for vitamin D metabolites (DEQAS) was set up in 1989. In 2013 DEQAS became an accuracy based EQA for 25-OHD with 'target values' assigned by the National Institute of Standards and Technology (NIST) Reference Measurement Procedure (RMP). A pilot scheme for serum 24,25(OH)2D3 was started in 2015 and participants were asked to measure the metabolite on each of the 5 samples sent out for 25-OHD. Inter-laboratory agreement was poor but this may reflect methodological differences, in particular different approaches to assay standardization. An important potential contribution to reducing variability among assays was the development by NIST of a 24,25(OH)2D3 RMP and its use in assigning values to SRMs 972a, 2973 and 2971, supported by the NIH Office of Dietary Supplements (ODS) as part of the Vitamin D Standardization Program (VDSP) effort.

Five-year follow up of a low glycaemic index dietary randomised controlled trial in pregnancy-no long-term maternal effects of a dietary intervention.

OBJECTIVE: To determine whether a dietary intervention in pregnancy had a lasting effect on maternal outcomes of diet, HbA1c and weight retention 5 years post-intervention; and to establish whether modifiable maternal behaviours were associated with these outcomes. DESIGN: Randomised control trial of low glycaemic index (GI) diet in pregnancy with longitudinal follow up to 5 years post-intervention. SETTING: Dublin, Ireland (2007-2016). POPULATION: In all, 403 women of 759 (53.1%) were followed up at 5 years. A total of 370 (intervention n = 188; control n = 182) were included in this analysis. METHODS: Fasting glucose was measured at 13 and 28 weeks' gestation and HbA1c (mmol/mol) at 5-year follow up. Weight retention (kg) from early pregnancy to 5 years post-intervention was calculated. Dietary intakes, anthropometry, and lifestyle factors were measured in pregnancy and 5 years post-intervention. Multiple linear regression models, controlling for confounders, were used for analysis. OUTCOME: Maternal diet, HbA1c, and weight retention at 5 years post-intervention. RESULTS: There was no difference between the intervention and control at 5 years post-intervention for any long-term maternal outcomes measured. HbA1c at 5 years post-intervention was associated with early-pregnancy fasting glucose (B 1.70, 95% CI 0.36-3.04) and parity ≥3 (B 1.04, 95% CI 0.09-1.99). Weight retention was associated with change in well-being from pregnancy to 5 years (B -0.06, 95% CI -0.11 to -0.02), gestational weight gain (B 0.19, 95% CI 0.00-0.38), and GI (B 0.26, 95% CI 0.06-0.46) at 5 years. CONCLUSIONS: The ROLO low-GI dietary intervention in pregnancy had no impact on maternal dietary intakes, HbA1c or body composition 5 years post-intervention. Maternal factors and lifestyle behaviours in pregnancy have long-term effects on glucose metabolism and weight retention up to 5 years later. TWEETABLE ABSTRACT: Pregnancy factors are associated with maternal glucose metabolism and weight retention 5 years later-findings from the ROLO Study.

Hydroxyvitamin D assays: An historical perspective from DEQAS.

Recent years have seen a substantial increase in demand for 25-hydroxyvitamin D (25-OHD) assays. DEQAS (the Vitamin D External Quality Assessment Scheme) has been monitoring the performance of these assays since 1989. The first DEQAS distribution was in June 1989 and results were submitted by 13 laboratories in the UK, two of which used HPLC/UV; the rest used ligand binding assays with a tritium tracer. Inter-laboratory CVs (ALTM) ranged from 29.3% (42.7nmol/L) to 53.7% (20.0nmol/L). Currently the scheme has participants in 56 countries using 30 methods or variants of methods. In January 2017, 918 participants returned results and inter-laboratory CVs (ALTM) ranged from 10.3% (73.1nmol/L) to 15.3% (29.4nmol/L). Over the last 27 years, there have been a number of significant milestones in assay development. The first major advance was the development of an iodinated 25-OHD tracer by Hollis and Napoli in 1992, subsequently used in an RIA kit marketed by DiaSorin. This and other commercial radioimmunoassays that followed brought 25-OHD assays within reach of many more non-specialist routine laboratories. With the introduction of fully automated non-isotopic assays without solvent extraction, measurement of 25-OHD became available to any clinical chemistry laboratory with an appropriate analytical platform. However, as the limitations of these non-extraction assays became apparent more laboratories started using LC-MS/MS methodology. Meanwhile the variable accuracy of 25-OHD methods has been addressed by the Vitamin D Standardization Program (VDSP) which encourages manufacturers to produce methods traceable to the reference measurement procedures (RMPs) of NIST, University of Ghent and the Centers for Disease Control and Prevention (CDC). DEQAS changed to an accuracy-based scheme in 2013 and now assesses assay accuracy against the NIST RMP. This review will use DEQAS results and statistics to chart the historical development in 25-OHD assay technology and highlight some of the problems encountered in obtaining reliable results for this most challenging of analytes.

Should Free Thyroxine Go Back into the Routine Thyroid Profile?

BACKGROUND: Many clinical chemistry laboratories offer thyroid-stimulating hormone (TSH) alone as a first-line test of thyroid function, and only reflex a free thyroxine (fT4) test if the TSH result is abnormal (i. e., outside of the laboratory reference range). In secondary hypothyroidism, a low fT4 may be accompanied by a low or a normal TSH level. A testing strategy that measures baseline TSH only risks missing cases of secondary hypothyroidism in which the TSH level is normal. METHODS: The current authors examined 26,106 consecutive thyroid function test (TFT) results in our initial analysis. If the TFT results were compatible with hypopituitarism, with fT4 below the reference range (9-20 pmol/L) and a TSH result ≤5 mU/L (reference range: 0.5-5 mU/L), the laboratory performed further tests of pituitary function. The cost of identifying pituitary insufficiency by measuring both fT4 and TSH was estimated for our population (in 2004 and 2013) and compared with 2 other relevant studies. RESULTS: A total of 121 patients had a normal TSH with a low fT4. 8 new cases of secondary hypopituitarism were identified when fT4 was combined with TSH as the front-line TFT profile. Of these, 5 were found to have pituitary adenomas, 2 of which were macroprolactinomas. The reagent cost of identifying each case by inclusion of fT4 in the TFT profile decreased from £11,568 (€16,089) in 1998 to £1451 (€2018) in 2013. CONCLUSIONS: 8 cases of pituitary insufficiency would not have been identified with a strategy of TSH testing alone, which calls for the addition of fT4 to the routine TFT profile. The cost per case of identifying those with pituitary insufficiency by additional measurement of fT4 has become cheaper with time.

How Useful are Laboratory Practice Guidelines?

Clinical practice guidelines (CPGs) relating to laboratory diagnostic testing are increasingly produced with the aim of standardizing practice and improving patient care based on the best available evidence. However, the production of a CPG is merely the first step in the process of getting evidence into practice, to be undertaken by laboratories and other stakeholders. This process should evaluate the information provided in the guidelines on laboratory tests, devise a strategy for implementing the CPG or the laboratory aspects of the CPG and finally, once implemented, assess the impact of the CPG on clinical practice, patient outcomes and costs of care. The purpose of CPG evaluation by the laboratory is to determine whether sufficient information is provided on the particular test recommended. CPGs may not always be written with the involvement of a laboratory specialist and this underlies the paucity of relevant information in some national guidelines. When laboratory specialists are involved, CPGs can provide practical information which supports local laboratories as well as clinicians in the implementation and appropriate use of recommendations. Implementation of CPGs is an often neglected area that needs attention and thought. There are many barriers to successful implementation, which may vary at local level. These need to be identified early if CPGs are to be successfully adhered to. The effectiveness of CPGs also needs to be audited using process and health outcome indicators. Clinical audit is an effective tool for assessing adherence to recommendations and for measuring the impact and success of the CPG.

Mitigation and detection of spurious potassium and sodium results.

Spurious laboratory results are results that are analytically correct but do not accurately reflect the in vivo plasma analyte concentrations. Spurious electrolyte results often lead to unnecessary testing or injudicious treatment and have an adverse effect on patient outcome. In this review we discuss the preanalytical and analytical variables that lead to spurious sodium and potassium results. We describe ways to detect them both in the laboratory and in clinical practice and suggest how to prevent them.

The relationship between gonadotrophic hormones and progesterone in the mid-luteal phase.

CONTEXT: It is known that progesterone (PRG) exerts a negative feedback on gonadotrophic hormones in the mid-luteal phase. However, we are unaware of any data in the literature that states the nature of this relationship, for example, is it linear or not? OBJECTIVE: To determine the relationship between gonadotrophic hormones and PRG in the mid-luteal phase using routine clinical assays and routine clinical patient data. METHODS: Retrospective mid-luteal phase serum follicle-stimulating hormone (FSH), leutinizing hormone (LH) and PRG data from 393 women were obtained from the laboratory computer system. Polynomial regression analysis was performed using this data to get the best fit curves. Using the best fit curve, the lowest PRG concentration on the linear phase of the best fit lines were determined with the corresponding gonadotrophic hormone concentrations. RESULTS: The expected inverse relationships were observed. However, polynomial regression curves provided better data fits than linear regression for both LH and FSH. A scatter about the best fit curves was noted for both FSH and LH with the data for LH having a grater scatter around the curve than FSH. The lowest PRG concentration on the linear phase of the best fit curves were 53 and 45 nmol/l for the LH and FSH curves respectively. The LH and FSH concentrations in the linear phase were 4.78 and 3.10 micro/l respectively. DISCUSSION: Our data shows that the relationships between LH or FSH and PRG are curvi-linear. Beyond PRG concentrations of 60 and 44 U/l, there is no further decrease in the LH and FSH concentrations respectively. These cut-offs could be physiologically significant. However, due to the large scatter around the curve, significant differences in FSH and LH concentrations may be found when such PRG concentrations are present and may include low concentrations.

Investigation of outpatients referred to a chemical pathologist with potential pseudohyperkalaemia.

BACKGROUND: Pseudohyperkalaemia is when the in vitro blood potassium concentration is artefactually raised while the in vivo concentration is normal. With unexplained hyperkalaemia, pseudohyperkalaemia needs to be excluded to avoid unnecessary and potentially detrimental therapy. There are numerous causes, but no systematic approach for the investigation of outpatients with potential pseudohyperkalaemia exists in the literature. AIMS: To evaluate the in-house protocol. METHODS: Patients referred for investigation of potential pseudohyperkalaemia underwent an outpatient based protocol which is designed to determine whether the cause was due to delayed blood separation, clotting, centrifugation or a haematological abnormality. RESULTS: 32 patients with serum potassium of 5.5-7.1 mmol/l were referred. All patients had pseudohyperkalaemia; the most frequent causes were full blood count (FBC) abnormalities (28%), time >4 hours from sampling to centrifugation (28%) and sample clotting (25%). Anaemia was more likely to be found in male patients. CONCLUSION: Before a problem can be treated, it must be confirmed and its aetiology identified. A systematic approach to investigate potential pseudohyperkalaemia has been presented. This confirmed the clinician's suspicion of pseudohyperkalaemia and in the majority of patients the aetiology was also identified. The use of serum and plasma potassium with an FBC in the initial investigation will identify whether clotting or a haematological abnormality is the cause in about half of the cases. Assay of whole-blood potassium is less important as centrifugation is a rare cause. Time to centrifugation is likely to play a major part in the majority of the remaining cases.

Comparison of reflective and reflex testing for hypomagnesaemia in severe hypokalaemia.

AIM: To compare the impact and effectiveness of introducing reflective and reflex testing of magnesium in severe hypokalaemia. METHODS: All specimens with [K] < or =2.5 mmol/l were retrospectively identified in three 6-month periods: baseline, with reflective testing, and with reflex testing. For each episode of hypokalaemia it was noted whether [Mg] was measured. RESULTS: Measurement of [Mg] increased from 7.7% to 63.9% (p<0.001) after introducing reflective testing, and then to 98.7% (p<0.001) with reflex testing. Diagnosis of hypomagnesaemia increased from 7.7% to 43.1% (p<0.001) and 69.3% (p<0.01) with reflective and reflex testing, respectively. For severe hypomagnesaemia ([Mg] <0.50 mmol/l) the increase was from 1.9% to 8.3% (p = 0.127 relative to baseline) with reflective testing and then to 12.0% with reflex testing (p<0.05 relative to baseline and p = 0.463 relative to reflective testing). The number of tests needed to diagnose was similar for reflective and reflex testing: 1.48 and 1.42 for hypomagnesaemia, respectively; and 7.67 and 8.22 for severe hypomagnesaemia, respectively. 42 and 70 extra magnesium assays compared to baseline were requested due to reflective and reflex testing, respectively. CONCLUSION: Reflex testing was the most time-efficient and consistent method of diagnosing hypomagnesaemia in severe hypokalaemia. This was mainly due to the increased number of magnesium assays performed. However, as the absolute increase in test numbers was small (28 in a 6-month period) and the test is inexpensive, selective reflex testing can improve quality in a cost-efficient manner.

Requesting patterns for serum calcium concentration in patients on long-term lithium therapy.

AIM: Long-term lithium therapy is associated with hypercalcaemia in 10-60% of patients, but unlike creatinine and thyroid stimulating hormone (TSH), monitoring by general practitioners of serum calcium for patients on lithium is not a requirement of the Qualities and Outcomes Framework (QOF) of 2004. We aimed to assess requesting patterns for serum calcium in patients on long-term lithium therapy and subsequent diagnosis of hypercalcaemia. METHODS: We identified 100 patients on long-term lithium therapy, as indicated by regular monitoring of lithium levels in our laboratory for at least 1 year. We determined how many of these patients had had serum calcium analysed, noting the assay date, concentration, source of request and clinical details stated. RESULTS: Forty-three out of hundred patients had serum calcium analysed during the course of their treatment including 28 in the previous 15 months. Twenty-one patients had serum calcium analysed by their GP, including 12 in the previous 15 months. Hypercalcaemia was diagnosed in five patients (11.6%). CONCLUSION: A significant proportion of patients in whom calcium was checked developed hypercalcaemia on lithium therapy. However, only 12% of the patients had serum calcium requested by their GP in the previous 15 months, which compares unfavourably with TSH and creatinine, for which monitoring approaches 100%. We recommend that serum calcium be checked every 15 months along with creatinine and TSH. This might be achieved by incorporating appropriate targets into the QOF, or by reflective or reflex adding-on of calcium to lithium specimens from patients who have not had calcium analysed in the previous 15 months.

Appropriateness of the National Academy of Clinical Biochemistry recommendation of repeating HbA1c analysis for extreme results in clinical practice.

BACKGROUND: The National Academy of Clinical Biochemistry (NACB) recommends that the presence of a variant or modified haemoglobin be considered when any HbA1c result is below the lower limit of the reference interval or >or=15%. In those instances where a variant haemoglobin is suspected, repeat measurement using an alternative method is the usual course of action. In the present study, we undertook to determine the impact of this guideline on our identification of variant and modified haemoglobins. METHODS: All requests for HbA1c estimation received over a 32-month period, and which gave a result of <4% or >15% were re-analysed by a different method and the results compared. RESULTS: Over the 32-month period, 94 samples with a HbA1c result of <4% or >or=15% were identified. Of these, 80 were re-analysed using a different method. No chromatographic abnormalities were seen and there were no significant differences between the results obtained using the two methods. CONCLUSIONS: No variant or modified haemoglobins were identified in this study and this observation is likely to be representative of the ethnic makeup of our patient population. On the basis of this finding, we recommend that laboratories consider local factors when deciding whether to comply with the NACB guidelines.